Abstract 6350: Very high PD-L1 expression as a prognostic indicator of overall survival amongst advanced non-small cell lung cancer patients receiving anti PD-(L)1 monotherapies in the first line setting: An IPW weighted health system analysis
Authors: Mohsin Shah, Rebecca A. Hubbard, Ronac Mamtani, Sean Hennessy
Journal: Cancer Research (2022)

Abstract Background Programmed death or ligand-1 (PD-(L)1) pathway inhibitors, a type of immunotherapy (IO), have become a standard anti-tumor strategy for advanced non-small cell lung cancer (aNSCLC) resulting in improved survival compared to platinum-doublet chemotherapy in PD-L1 expression (PD-L1+e ≥50%) in the 1L treatment setting. Limited evidence to suggest that amongst aNSCLC patients with PD-L1+e of 50%-100%, very high levels of PD-L1e (≥90%) would have any additional prognostic value leading to improved outcomes. Identifying additional PDL1+e cutoffs in aNSCLC with PDL1+e of 50%-100% would help treatment selection in routine practice as well as future IO clinical trials design ensuring trial groups are evenly balanced based on PD-L1+e levels. Objective To assess very high PD-L1+e (≥90%) as a prognostic indicator of overall survival in aNSCLC patients with PDL1+e ≥50% receiving anti PD-(L)1 monotherapies, using a single university EMR based health database. Methods Cohort study of aNSCLC patients, who initiated IO monotherapy in the 1L treatment setting from October 2016, to August 2021, and had a PDL1+e ≥ 50%. This study was conducted in the University of Pennsylvania Health System. Patients with incomplete treatment data or those harboring sensitizing alterations in EGFR, ALK, or ROS1 genes were excluded. The primary outcome was overall survival, measured from the start of 1L IO monotherapy (index date) to date of death or last confirmed activity. Propensity score-based inverse probability weighting (IPW) was used to address confounding in KM curves and Cox hazard regression. Baseline characteristics included age at therapy initiation, race, gender, smoking status, tumor histology, presence of KRAS or BRAF mutation, and ECOG PS. Results 196 aNSCLC receiving IO monotherapy met the inclusion criteria; n=30 had missing ECOG PS. 53% of the cohort were female, the median age at therapy initiation was 68 years, 72% had non-squamous cell carcinoma with 92% having a history of smoking, 28% had a KRAS mutation, and 37% had very high PDL1+e. Covariates were well balanced between groups after IPW weighting (all │standardized differences│&amp;lt;0.1). 92% received Pembrolizumab IO monotherapy. Median overall survival was 3.85 years (v high -PDL1+e) vs 1.52 years (high -PDL1+e), respectively. In the complete case analysis (n=166), having a very high PDL1+e (HR 0.57, 95% CI 0.36-0.90) was associated with lower mortality. Study limitations include the potential for unmeasured confounding and potentially limited generalizability. Conclusion Patients with aNSCLC having very high PDL1+e (≥90%) receiving IO monotherapy appear to have improved survival in the 1L setting. These findings should be confirmed in a larger real-world data set. Citation Format: Mohsin Shah, Rebecca A. Hubbard, Ronac Mamtani, Sean Hennessy. Very high PD-L1 expression as a prognostic indicator of overall survival amongst advanced non-small cell lung cancer patients receiving anti PD-(L)1 monotherapies in the first line setting: An IPW weighted health system analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6350.